Asbestosis in humans is associated with alteration of the humoral and cellular immune responses. It is not clear if these systemic findings are non-specific epiphenomena or indicative of the immune system's involvement in the inflammatory response and fibrosis of the lung. The purpose of this project is to define the nature and sequence of the immunologic, cellular and histologic events in the lung which occur during inhalation of asbestos. Particular attention will be focused on the early events after initiating the exposure. The inflammatory mechanisms analyzed will be correlated to histology, aerosol fiber characteristics and lung fiber burden. Evaluating this early inflammatory response will not only examine the mechanisms of inflammation, but inflammatory mediator(s) may be identified as a 'marker' for the eventual development of fibrosis. Fischer-344 rats will be exposed to aerosolized chrysotile asbestos for 7 hours/day with serial increases in the duration of the exposure: 1, 3, 5, 9 and 12 days. At termination of the exposure the animals will be sacrificed periodically over two weeks, at six months and one year. Systemic immune response will be measured by C3 protein activity and immunoglobulin levels. Bronchoalveolar lavage (BAL) will be assayed for C3, immunoglobulins, and functional assays for humoral mediators of cell activation: (1) chemotactic factors for polymorphonuclear and mononuclear cells, (2) fibroblast growth factor, (3) factors mitogenic to T lymphocytes. These functional assays will also be done on supernatants from cultured alveolar macrophages to determine if functional activity seen in the BAL is originating from the macrophage. Co-culture assays of lymphocytes, macrophages, and fibroblasts will be conducted to evaluate lymphokine mediated fibroblast growth during the same time sequence as the inflammatory mediators. These assays will be evaluating the sequence of inflammatory events and identifying mediators critical to developing lung injury. The presence of certain mediators may identify the point at which the injury becomes irreversible, possibly due to a critical lung fiber burden which may induce these mechanisms of lung injury. A 'marker' may be identified which may have application in the detection of early stages of lung injury in humans when avoidance or intervention might be undertaken.